Bacterial infections, especially bacterial infections of the respiratory tract, are a major problem for production animals such as cattle, pigs, sheep, and other livestock. Bacterial infections are also a common problem with companion animals such as cats, dogs, and horses. Bacterial infections are typically treated using antibiotics.
A class of broad spectrum antibiotics classified as D-(threo)-1-p-substituted phenyl-2-halogenoacetylamido-1,3-propanediols are known in the art. This class of antibiotics includes chloramphenicol(D-(threo)-1-p-nitrophenyl-2-dichloroacetamido-1,3-propanediol), thiamphenicol(D-(threo)-1-p-methylsulfonylphenyl-2-dichloroacetamido-1,3-propanediol), fluorthiamphenicol(D-(threo)-1-p-methylsulfonylphenyl-2-difluoroacetamido-1,3-propanediol) and tevenel(D-(threo)-1-p-aminosulfonylphenyl-2-dichloroacetamido-1,3-propanediol) (See, U.S. Pat. No. 4,235,892 to Nagabhushan). Replacing the primary hydroxyl group at C-3 of chloramphenicol by chlorine or bromine, however, destroys the biological activity thereof (F. E. Hahn, Antibiotics, Ed. Gottlieb and Shaw, Springer-Verlag, New York, (1967), p. 308; F. E. Hahn et al, Antibiotics and Chemotherapy, 6, No. 9, 531 (1956); L. Cima and A. Ilecto, II Farmaco, Ed. Sc. 12, No. 6, 535 (1957); S. Mitsuhasi et al, Jap. J. Microbial. 13, No. 2, 177-80 (1969); M. Kono et al, Jap. J. Microbiology 15 (3), 219-27 (1971); and U.S. Pat. No. 4,235,892 to Nagabhushan).
U.S. Pat. Nos. 4,235,892; 4,311,857; and 4,677,214 disclose D-(threo)-1-aryl-2-acylamido-3-fluoro-1-propanol compounds that are allegedly useful as antibiotics. Florfenicol, [(R-(R*,S*)]-2,2-dichloro-N-[1-fluoromethyl)-2-hydroxy-2-[4-(methylsulfonyl)phenyl]ethyl]acetamide or D-threo-2,2-dichloro-N-[1-(fluoromethyl)-2-hydroxy-2-[4-methylsulfonyl) phenyl]ethyl]-acetamide), commercially available from Schering-Plough Animal Health, New Jersey as NUFLOR®, is an example of an antibiotic in this class of compounds.
United States published patent application no. US 2003/0216447 and United States published patent application no. US 2003/0220302 each disclose compositions comprising flunixin and a florfenicol or florfenicol-like compound that are allegedly useful for treating microbial infections in animals.
International publication WO 03/077828 discloses fluorfenicol 1-type antibiotics that allegedly exhibit antimicrobial activity.
US 2005/0075506 discloses a process for preparing florfenicol that involves forming an oxazolidine compound from a 1-phenyl-3-hydroxy-2-amino-1-propanol compound and fluorinating the oxazolidine compound.
U.S. Pat. Nos. 4,743,700; 5,332,835; 5,153,328; and 5,567,844 each disclose a method for replacing the fluorine of the primary hydroxy group of a 1-phenyl-2-amino-1,3-propanediol compounds by protecting the secondary hydroxy group and the amino group and fluorinating with inorganic fluoride in polyglycol. The secondary hydroxy group and the amino group can be protected as an oxazoline.
U.S. Pat. No. 5,352,832 discloses a stereospecific process for preparing florfenicol, thiamphenicol, and chloramphenicol having the correct relative and absolute stereochemistry from achiral trans-cinnamic acid derivatives.
U.S. published application no. US 2005/0075506 discloses a process to prepare florfenicol from (1R,2R)-2-amino-1-[(4-methylsulfonyl)phenyl]-1,3,propanediol that involves forming an oxazolidine intermediate.
U.S. Pat. No. 5,663,361 discloses a method for making an ozazoline intermediate useful for preparing florfenicol.
U.S. Pat. No. 5,382,673 discloses a method for making florfenicol that involves formation of an ozazoline intermediate.
U.S. Pat. Nos. 5,105,009; 5,908,937; and 5,243,056 each disclose a method for preparing 1-(phenyl)-1-hydroxy-2-amino-3-fluoro-propane derivatives via an oxazolidine intermediate.
U.S. Pat. No. 5,789,599 discloses N-sulfinyl-2-carboxyaziridine compounds and the synthesis of florfenicol, thiamphenicol, and chloramphenicol from the N-sulfinyl-2-carboxyaziridine compounds.
U.S. Pat. No. 4,582,918 discloses the preparation of cis-1-aryl-2-(fluoromethyl)oxiranes and there use in preparing (threo)-1-aryl-2-acylamido-3-fluoro-1-propanols.
U.S. Pat. No. 5,556,829 discloses amide compounds that are useful in agriculture as herbicides in the defense of useful crops from weeds.
There is a need in the art, however, for improved methods of preparing this class of antibiotics, i.e., D-(threo)-1-aryl-2-acylamido-1-propanol compounds, D-(threo)-1-aryl-2-acylamido-3-fluoro-1-propanol compounds, and D-(threo)-1-aryl-2-acylamido-3-hydroxy-1-propanol compounds. The present invention addresses this need.
Citation of any reference in this section of this application is not to be construed that such reference is prior art to the present application.